蛋氨酸负荷试验在糖尿病周围神经病变中的临床意义

目的评估蛋氨酸负荷试验(MLT)与糖尿病周围神经病变的关系。方法选空腹血浆同型半胱氨酸(Fhcy)水平在正常范围(≤15 mmol/L)内的103例2型糖尿病患者,分为糖尿病周围神经病变(DPN )组和无糖尿病神经病变(DPN-)组,另50例健康体检者作为对照(CON)组,于MLT后行Hcy(Phcy)测定,按体重0.1g/kg口服蛋氨酸,并测取服药前后4 h血同型半胱氨酸(Hcy)及糖化血红蛋白(HbAlc)、甘油三酯(TG)、胆固醇(TC)等水平。结果Phcy水平DPN 组[(37.3±1.3)mmol/L]明显高于DPN-组[(25.0±1.2)mmol/L]及CON组[(9.8±1.4)mmol/L,P<0.01];餐后2 h血糖(PPG)、TG水平均DPN 组高于DPN-组及CON组,差异有统计学意义(P<0.05),而叶酸(FA)、维生素B12(Vit B12)水平则DPN 组低于DPN-组及CON组(P<0.01)。结论高Hcy(Hhcy)及低FA、VitB12水平与2型DM患者伴发周围神经病变相关,在DPN 组患者中进行MLT检查有助于Hhcy血症及早发现。     

2型糖尿病周围神经病变的危险因素分析及与血清C肽水平的相关性研究

目的观察2型糖尿病周围神经病变(Diabetic Peripheral Neuropathy,DPN)患者行口服葡萄糖耐量试验后不同时间点血清C肽(C-peptide,CP)水平的变化及临床意义。方法入选176例2型糖尿病患者,根据是否存在DPN分为单纯糖尿病(SDM)组66例和DPN组110例。采用散射比浊法测定血清CP水平,比较两组间临床指标及CP水平,并分析DPN发生的危险因素。结果 (1)两组间单因素比较,DPN组病程、年龄、尿微量白蛋白/肌酐、D-二聚体、空腹血糖、糖化血红蛋白(Hb A1c)水平较SDM组高,DPN组体重指数(BMI)、空腹C肽(Fasting C-peptide,FCP)、胰岛素抵抗指数较SDM组水平低。(2)经重复测量方差分析,两组间C肽无差异,尚未发现时间与组别间存在交互作用,不同时间点进一步做两两比较,各个时间点间差异均有统计学意义,随着时间的延长C肽逐渐上升,2 h达到高峰,3 h下降。(3)Logistic回归分析显示病程、年龄、BMI、Hb A1c、糖尿病肾脏病是DPN发生的独立危险因素。结论 2型糖尿病患者发生DPN时FCP水平下降,口服葡萄糖耐量试验后的SDM与DPN两组间C肽无差异,病程、年龄、BMI、Hb A1c、糖尿病肾脏病是DPN发生的独立危险因素。     

心力衰竭患者抑郁状况及相关因素

目的探讨心力衰竭患者的抑郁状况及相关的影响因素。方法采用自制的一般资料表及流调中心抑郁自评量表(Centre of Epidemiological Studies-Depression scale,CES-D)对132名心力衰竭患者进行调查。结果心力衰竭患者的抑郁检出率为49.2%,CES-D分为15.96±8.71,均高于我国城市常模(χ~2=14.95,P0.001;t=3.02,P=0.003);并发慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)、并发高血压及血清25(OH)D浓度50 nmol/L的心力衰竭患者的抑郁发生率均高于未并发COPD、未并发高血压及血清25(OH)D浓度≥50 nmol/L的患者(χ~2=4.78,P=0.029;χ~2=5.92,P=0.015;χ~2=18.69,P0.001);具有抑郁症状心力衰竭患者与不具有抑郁症状的患者相比,其血清25(OH)D浓度偏低(t=-9.53,P0.001),而血清NT-proBNP浓度偏高(t=6.10,P0.001);相关分析显示,心力衰竭患者的抑郁状况与血清25(OH)D浓度呈负向相关(r=-0.31,P=0.014),与血清NT-proBNP浓度正向相关(r=0.29,P=0.006)。结论心力衰竭患者的抑郁发生率较高;心力衰竭患者抑郁的危险因素有:并发高血压、并发COPD、血清25(OH)D浓度降低(50 nmol/L)及血清NT-proBNP浓度升高。     

2型糖尿病视网膜病变患者血清25(OH)D3血管内皮生长因子整合素αvβ3的表达

目的 研究2型糖尿病患者血清25(OH)D3、血管内皮生长因子(VEGF)、整合素αvβ3的水平及在预测糖尿病视网膜病变(DR)发生发展中的临床意义。方法 选取2019-03-06在郑州大学第二附属院住院的189例T2DM患者,分为无DR组(NDR组52例)和有DR组(DR组137例),收集2组临床资料,检测血清25(OH)D3、VEGF、整合素αvβ3的表达水平。结果血清25(OH)D3水平与年龄、BMI、HbA1c、FINS、FPG、VEGF、整合素αvβ3、有无糖尿病视网膜病变均呈明显负相关,VEGF与整合素αvβ3呈正相关(均P0.05);病程、BMI、SBP、整合素αvβ3水平水平是DR的危险因素,25(OH)D3是DR的保护因素;当VEGF及整合素αvβ3分布大于预测界值24.22pg/mL和5.19ng/mL时,ROC曲线下面积分布为0.60(95%CI 0.503～0.696)、0.671(95%CI 0.571～0.771),预测价值最大。结论 随着DR的发展,血清25(OH)D3水平逐渐降低,VEGF水平逐渐升高,整合素αvβ3水平随之升高,提示25(OH)D3、VEGF、整合素αvβ3共同参与了DR的发生、发展。     

抑郁症患者血清维生素D水平的研究

目的:探讨抑郁症患者血清维生素D水平及其与抑郁症病情的相关性。方法:随机抽取门诊抑郁症患者80例(抑郁症组),以电发光化学法测定血清25(OH)D3;并与50名性别、年龄相匹配的体检者(对照组)比较;采用汉密尔顿抑郁量表(HAMD)24项对抑郁症患者进行评估,分析血清25(OH)D3水平与HAMD评分的关系。结果:抑郁症组血清25(OH)D3[(25.54±7.09)ng/ml]明显低于对照组[(42.03±10.21)ng/ml](P0.01);抑郁症组血清维生素D不足率(60%)或缺乏率(25%)明显高于对照组(8%,0)(P均0.01);抑郁症患者血清25(OH)D3水平与HAMD评分呈负相关(r=-0.73,P0.01)结论:抑郁症患者血清维生素D水平降低,并与其病情相关。     

糖尿病周围神经病变患者腓肠神经与跟腱病变的超声测值变化及相关性研究

目的探讨2型糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)患者腓肠神经与跟腱病变的超声测值变化及相关性。方法运用高频超声观察分析42例2型糖尿病伴DPN患者、42例T2DM(Type 2Diabetes Mellitus,T2DM)不伴有DPN患者及42例非糖尿病健康成人腓肠神经和跟腱内部结构及周边组织情况,测量腓肠神经横截面积和跟腱近止端厚度。比较各组间腓肠神经横截面积和跟腱近止端厚度测值,并对两者进行Pearson相关性分析及散点图呈现。结果 DPN组异常声像图显示率明显高于NDPN组,DPN组检出有异常声像图例数为35例,占83. 33%,无DPN组检出有异常声像图改变为14例,占33. 33%。DPN组的腓肠神经横截面积、跟腱厚度值较NDPN组和非糖尿病组增大,且差异有统计学意义(P 0. 05)。DPN患者腓肠神经截面积与跟腱厚度呈正相关(r=0. 747,P 0. 05)。结论糖尿病周围神经病变患者腓肠神经及跟腱病变发生率高,高频超声有助于发现DPN患者腓肠神经及跟腱病变,二者在协同评估DPN病变中有重要的价值。     

多发性硬化患者血清维生素D水平变化及与临床相关性研究

目的观察多发性硬化(MS)患者体内维生素D水平,探讨维生素D水平与MS临床表型的关系。方法收集MS患者72例,包括复发缓解型MS(RRMS)62例、继发进展型MS(SPMS)7例及原发进展型MS(PPMS)3例;视神经脊髓炎(NMO)患者24例;以32名健康体检者为健康对照组(NC组)。采用电化学发光法对血清25-羟维生素D_3[25-hydroxyvitamin D_3,25(OH)D_3]进行检测,所有MS患者在留取血标本的同时进行扩展残疾状态量表(EDSS)评分,对其中15例急性复发期RRMS患者在缓解期再次行血清25(OH)D_3检测和EDSS评分。结果 MS组、NC组及NMO组间血清25(OH)D_3水平比较差异有统计学意义(F=10.55,P0.01),MS组及NMO组均低于NC组(分别P0.01,P0.05),但MS组与NMO组相比差异无统计学意义(P0.05);SPMS患者血清25(OH)D_3水平低于NC组(P0.01),但与RRMS患者比较无统计学差异(P0.05);RRMS患者血清25(OH)D_3水平缓解期高于急性复发期(t=2.92,P0.05),但仍低于NC组(P0.01)。结论 MS及NMO患者体内维生素D不足,且维生素D不足贯穿于MS的不同病程阶段,RRMS患者急性复发期维生素D不足更为明显。     

25羟基维生素D与脑梗死体积的相关性研究

目的探讨25-羟基维生素D[25-hydroxyvitamin D,25(OH) D]与急性缺血性卒中梗死体积的相关性。方法收集2017年1月-2018年12月在包头医学院第二附属医院神经内科住院的急性缺血性卒中患者174例,卒中筛查门诊资料完整健康中老年人186例。根据头部核磁梗死体积分为3组:小体积组(梗死体积≤1 cm3)、1 cm3中体积组20 cm3、和大体积组(梗死体积≥20 cm3)。分析3组之间在25(OH) D及外周血生化指标等方面是否有差异。以梗死灶体积分组为因变量,颈动脉内膜中层厚度分组及血管狭窄分组作为混杂因素,25(OH) D分组作为自变量,进行多元有序Logistic回归分析。结果 25(OH) D在3组之间(14. 51±4. 10 ng/L、12. 15±3. 30 ng/L、9. 67±2. 61 ng/L)差异有统计学意义(P=0. 000)。多元有序Logistic回归分析,排除混杂因素后,25(OH) D缺乏组、不足组与正常组相比,梗死体积增加一个等级的可能性分别是正常组的2. 826(P=0. 020)、1. 146(P=0. 764)倍。结论 25(OH) D的缺乏与患者的梗死体积的增大有关。     

热性惊厥患儿血清miR-148a-3p HMGB1 25(OH)D水平与癫痫发作的相关性

目的探讨热性惊厥患儿血清微小RNA-148a-3p (miR-148a-3p)、高迁移率族蛋白B1(HMGB1)、25-羟维生素D(25(OH)D)水平与癫痫发作的相关性。方法 回顾性分析2018-01—2022-03南阳市中心医院收治的122例热性惊厥患儿,根据热性惊厥患儿预后结局是否发生癫痫,分为热性惊厥癫痫组36例和热性惊厥非癫痫组86例,同期选择55例未发生惊厥的呼吸道感染仅发热的患儿为对照组,比较3组患儿的血清miR-148a-3p、HMGB1、25(OH)D水平。收集3组患儿临床资料进行多因素Logistic回归分析,绘制ROC曲线分析miR-148a-3p、HMGB1、25(OH)D对热性惊厥患儿癫痫发作的预测价值。结果热性惊厥癫痫组的血清miR-148a-3p表达量、HMGB1水平高于热性惊厥非癫痫组、对照组[（2.26±0.57）vs(1.71±0.43)vs(1.50±0.38);(7.45±1.87)μg/L vs(6.70±1.58)μg/L vs(5.33±1.29)μg/L;均P<0.05],血清25(OH)D水平低于热性惊厥非癫痫组、对照组[（26....     

GA/HbA1c比值与2型糖尿病周围神经病变相关性研究

目的 研究2型糖尿病患者血GA/HbA1c比值与糖尿病周围神经病变的相关性。方法 选取2018-12-2019-11在福建中医药大学附属人民医院住院的糖尿病患者681例。随机分为2型糖尿病不伴周围神经病变(NDPN)组366例,2型糖尿病周围神经病变(DPN)组315例。结果 NDPN组与DPN组年龄、病程、BMI、HbA1c、GA、GA/HbA1c、TG比较差异有统计学意义(P0.05)。DPN组患者合并心血管病、糖尿病肾病及糖尿病视网膜病变的比例明显高于NDPN组,差异有统计学意义(P0.05)。Logistic回归分析显示,病程、GA/HbA1c、合并糖尿病肾病及糖尿病视网膜病变是DPN独立危险因素。ROC曲线显示,HbA1c曲线下面积(AUC)为0.601,Cut-off值为8.05%(敏感性65.2%,特异性51.8%);GA曲线下面积(AUC)为0.706,Cut-off值为24%(敏感性70.6%,特异性62%);GA/HbA1c曲线下面积(AUC)为0.763,Cut-off值为2.82(敏感性81.6%,特异性65.1%)。结论 GA/HbA1c可能是预测糖尿病周围神经病变良好指标。     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

Anticonvulsant Drugs and Cognitive Function: A Review of the Literature

Summary: Alterations of cognitive function are separate from disturbances of behavior seen in association with epilepsy. The nature of the cognitive disability may to a certain extent depend on the seizure type. Partial seizures, mainly derived from a temporal lobe focus, impair memory tasks, while generalized seizures seem to have more effect on attentional abilities. A number of studies, reviewed in this paper, suggest that anticonvulsant drugs further impair cognitive function. Maximal impairments are seen in patients receiving polytherapy: rationalization of polytherapy improves cognitive abilities. Studies in children and adults have allowed differentiation of the effects of various commonly used antiepileptic agents. Maximal cognitive deficits are seen with. phenytoin, while phenobarbital and sodium valproate induce moderate disturbances, and carbamazepine seems relatively free from such toxicity. Further research is needed on the interrelationship between types of seizure disorders, types of anticonvulsant medications, and cognitive function.     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Effects of NMD A- and AMPA-Receptor Antagonists on Different Forms of Epileptiform Activity in Rat Temporal Cortex Slices

Summary: Lowering extracellular magnesium induces different patterns of epileptiform activity in rat hippocampus and entorhinal cortex. Short recurrent epileptiform discharges in the hippocampus are stable over time, whereas seizurelike events (SLEs) in the entorhinal cortex, the subiculum, and the neighboring neocortex develop into late recurrent discharges which are not blocked by clinically employed antiepileptic drugs. We tested the sensitivity of the different epileptiform discharge patterns to. /V-methyl-D-aspartate (NMDA)- and non-NMDA-receptor antagonists. As NMDA-receptor antagonist we used dextrorphan, ket-amine, and 2-aminophosphonovalerate (2APV); as α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-receptor antagonist we employed the quinoxaline derivative glutamate 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The findings show that the different patterns of epileptiform activity, including the late recurrent discharges, are sensitive to all NMDA-receptor antagonists. However, when dextrorphan was employed to suppress seizure-like events, later recurrent discharges did not develop during the remaining time course of the experiment. CNQX reversibly suppressed recurrent discharges in the hippocampus and SLEs in the entorhinal cortex. However, late recurrent discharges become insensitive to CNQX, even at a high concentration of 60 μM m. This finding suggests a prominent role for NMDA receptors in the generation of late recurrent discharges.